Objectives. The protocol is focused on the immune and inflammatory reactions in Alzheimer's disease (AD) and the possibility that blocking the inflammatory response may alter the course of the illness. The specific plan is to evaluate the biologic and clinical effects of two doses of cyclophosphamide (CY) immunotherapy in AD patients compared to the clinically available cyclooxygenase-2 inhibitor (COX-2), rofecoxib. The study will test the hypotheses that CY: 1) Is safe and tolerable in AD patients in meaningful clinical doses, 2) Can modify central nervous system inflammation and immune responses in AD, 3) Inhibits neurodegeneration in AD brains as indicated by peripheral biomarkers of AD pathology, and 4) Is different quantitatively or qualitatively in its effect on immune markers than placebo or other clinically-available anti-inflammatory drugs such as the COX-2 inhibitor, rofecoxib.